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The Tumor Microenvironment

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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

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Related Experiment Video

Updated: Oct 7, 2025

Assessing Tumor Microenvironment of Metastasis Doorway-Mediated Vascular Permeability Associated with Cancer Cell Dissemination using Intravital Imaging and Fixed Tissue Analysis

Assessing Tumor Microenvironment of Metastasis Doorway-Mediated Vascular Permeability Associated with Cancer Cell Dissemination using Intravital Imaging and Fixed Tissue Analysis

Published on: June 26, 2019

Vascular Microenvironment, Tumor Immunity and Immunotherapy.

Zachary Lamplugh¹, Yi Fan¹

¹Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, United States.

Frontiers in Immunology

|January 6, 2022

Summary

Tumor blood vessels create an immunosuppressive environment, hindering cancer immunotherapy. Reconditioning these tumor vasculature cells may enhance treatment effectiveness for solid tumors.

Keywords:

T cells endothelial cells exhaustion immune suppression immunity immunotherapy infiltration tumor microenvironment

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Author Spotlight: Creating Human Vascularized Micro-Tumors as Models for Translational Cancer Research

Author Spotlight: Creating Human Vascularized Micro-Tumors as Models for Translational Cancer Research

Published on: September 15, 2023

Area of Science:

Oncology
Immunology
Cancer Biology

Background:

T cell-based immunotherapy faces challenges in solid tumors due to limited tumor-specific antigens and an immunosuppressive tumor microenvironment (TME).
Abnormal tumor vasculature contributes to an immune-hostile microenvironment, promoting tumor resistance to immunotherapy and necessitating adjuvant treatment strategies.

Purpose of the Study:

To review the mechanisms by which the vascular microenvironment mediates tumor immune evasion and immunotherapy resistance.
To explore opportunities and challenges in targeting tumor vasculature for improved cancer immunotherapy.
To propose genetic programming of tumor endothelial cells as a novel approach to overcome immunotherapy resistance.

Main Methods:

Literature review focusing on molecular and cellular mechanisms of tumor vasculature-mediated immune suppression.
Analysis of aberrant vascularity, dysfunctional adhesion, immunosuppressive niche, and microenvironmental stress in the TME.
Discussion of potential therapeutic strategies targeting tumor endothelial cells.

Main Results:

Tumor vascular abnormalities, including dysfunctional adhesion and an immunosuppressive niche, facilitate tumor evasion of immune responses.
Microenvironmental stress within tumor vasculature contributes significantly to resistance against immunotherapy.
Genetic programming of tumor endothelial cells presents a promising avenue for reconditioning the vascular microenvironment.

Conclusions:

The tumor vascular microenvironment is a critical determinant of immunotherapy efficacy in solid tumors.
Targeting aberrant tumor vasculature offers significant potential for enhancing cancer immunotherapy outcomes.
Reprogramming tumor endothelial cells represents a novel strategy to overcome immunotherapy resistance.